# Adenosine deaminase mediates endothelial inflammation via an ADA1-CD26 interaction in post-COVID

## TL;DR

This study shows that adenosine deaminase (ADA1) contributes to vascular inflammation in post-COVID-19 syndrome by interacting with CD26 on endothelial cells.

## Contribution

The paper identifies a novel ADA1-CD26 interaction mechanism linking endothelial inflammation to post-COVID-19 syndrome.

## Key findings

- Post-COVID sera increase ADA1 and CD26 levels in lung endothelial cells.
- Inhibiting ADA1-CD26 reduces immune cell adhesion to endothelial cells.
- SARS-CoV-2 spike protein co-localizes with CD26 in activated endothelial cells.

## Abstract

Adenosine deaminase (ADA) isoenzymes play a role in microvascular dysfunction following SARS-CoV-2 infection. This study analyzes the mechanisms behind ADA1-dependent endothelial inflammation in post-COVID-19 syndrome. We investigated whether immune cells from post-COVID patients could contribute to the increased total ADA activity. Additionally, we examined ADA’s enzymatic and extra-enzymatic activities in human primary lung microvascular endothelial cells (HULECs) stimulated with post-COVID patients’ serum.

Treatment of HULECs with sera from post-COVID patients resulted in elevated levels of the ADA1 isoenzyme and the ADA1-anchoring protein, CD26. This increase correlated with enhanced adhesion of THP-1 monocytes/macrophages to HULECs. Inhibiting the ADA1-CD26 interaction with glycoprotein-120 prevented the rise in cell-surface ADA levels in HULECs and reduced the adhesion of THP-1 cells to the endothelium. A similar effect was observed when HULECs were pre-incubated with the SARS-CoV-2 spike protein, which co-localized with CD26 in activated HULECs.

We propose that ADA1 promotes vascular inflammation in post-COVID-19 syndrome through both canonical and non-canonical mechanisms. On one hand, its increased enzymatic activity can suppress adenosine-dependent pathways. On the other hand, ADA1 may function as an adhesion molecule facilitating interactions between immune cells and the endothelium via ADA1-CD26 complexes.